Etoposide (VP16-213), a semi-synthetic anti-tumor drug, is used effectively for the treatment of acute monocytic leukemia (Schilling's leukemia) as well as medullary monocytic leukemia, and has also been proved to be effective to a certain extent for treatment of recticulum cell sarcoma, tissue-cellular lymphoma, lymphosarcoma and Hodgkin's disease. In the therapy for solid carcinoma, etoposide has shown potent activity to small cell carcinoma of lung as well as testical cancer, and is said to be also effective against mastocarcinoma, carcinoma of urinary bladder and thyroid cancer. This drug may be used in combination with a variety of the other antitumor agents, to result in more satisfactory anti-tumor efficacy.
Some synthetic processes have been proposed in the previous literatures such as that reported by kuhn, Max et al in Swiss Pat. 514,578 (1971), which showed the following reaction Scheme (1) ##STR1##
It can be seen the above process includes long reaction pathway, a complex procedure and provides a low yield (only 18% based on 4-demethylepipodophyllotoxin).
Kurabayashi and Kalsuhiko et al reported in JP84-98098 another synthetic process, which included the following reactions (Scheme 2). ##STR2##
As compared with the above described method of Max et al, appreciable improvements in this synthetic process are obtained, such as the utilization of same protective group for both the phenolic hydroxy and the hydroxy groups in the sugar moiety, shorter reaction pathway, increased yield. However, Reaction Scheme (2) presents inconveniences. For example, strict conditions are required for controlling monoacylation of the phenolic hydroxy from compound 7 to 17. As such, it follows that the process should be improved.